This application relates generally to nanoparticulate compositions useful as diagnostic imaging agents for use in one or more of X-ray/Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). More particularly, the application relates to nanoparticulate compositions useful as contrast agents, and methods for making and using such agents.
Almost all clinically approved diagnostic contrast agents are compositions comprising small molecules. Relatively small, iodinated aromatic compounds have served as the standard contrast agents in X-ray and CT, while Gd-chelates are used for Magnetic Resonance Imaging. Known contrast agents suffer from one or more disadvantages such as overly rapid clearance from the body, overly long retention within the body, toxicity, no specificity, instability, and high cost. Such limitations work to reduce the overall effectiveness of a program of therapy relying on diagnostic imaging. Despite considerable progress made in this field to date there remains a need for new classes of contrast agents which overcome one or more of these disadvantages and/or which possess characteristics which enable new modes of diagnostic imaging.
Nanoparticulate compositions show considerable promise in medical applications, both diagnostic and therapeutic. While only a few nanoparticulate composition-containing agents have been clinically approved for magnetic resonance imaging applications and for drug delivery applications, hundreds of such agents are still in development. There is substantial evidence that nanoparticulate compositions have benefits over currently used small molecule agents in terms of efficacy for diagnostics and therapeutics. However, the effect of particle size, structure, and surface properties on the in-vivo bio-distribution and clearance of nanoparticulate composition-based agents is not well understood. Nanoparticles, depending on their size, tend to stay in the body for longer periods compared to small molecules. In the case of contrast agents, it is preferred to have maximum renal clearance of the agents from the body with minimum short term or long term toxicity.
Thus there is a need for new nanoparticulate compositions for use as contrast agents and/or imaging agents with improved properties. In particular, nanoparticulate compositions having improved characteristics related to renal clearance and toxicity would be especially advantageous. In addition, there is a need for novel synthetic intermediates with which to prepare such nanoparticulate compositions.